We have demonstrated the presence of collagenolytic activity in the livers of mice infected with Schistosoma mansoni cercariae; peak activity was reached approximately 8 weeks after infection and thereafter decreased. Maximal enzymatic activity coincided with the known peak of host cellular immune response. Enzymatic activity was isolated from a liver homogenate prepared after removal of granulomas by sedimentation and also from the culture medium in which activity was released from the granuloma explant. The explanted parasite eggs in the same culture medium did not release these activities. The collagenolytic activity was found to have the usual characteristics of a mammalian collagenase, and activities from both the liver and granulomas were similar. The enzyme was associated with 3 proteins of different molecular weight as determined by gel filtration; these were approximately 90,000, 42,000 and 21,000 daltons with specific enzyme activities of respectively 180, 750, 70 units per mg of protein. We propose to study whether these activities are elaborated by different specific cells or are 3 forms of one enzyme produced by one type of cell. We want to identify the cellular localization of enzyme production by immunofluorescent techniques using antibody raised aganist purified enzyme. Since our results tentatively indicate that the enzyme may be produced at least in part by macrophages, we want to determine whether the enzyme production can be stimulated by endotoxin or lymphokines and regulated by prostaglandins. Whether the subsequent decrease in enzymatic activity observed by us in livers of infected mice is due to removal of these substances or presence of unidentified inhibitors will be studied. We shall also study whether the stimulation of ongoing collagenase activity by simultaneous presence of these substances can prevent collagen accumulation and thereby permit some reversal of the liver fibrosis caused by schistosomiasis.